Further to previous
observations on the clear differences between ME/CFS and fibromyalgia already
provided for the MRC’s consideration, two additional points may be of relevance.

In
1994, the British Medical Journal published information from Dr Darrel Ho-Yen,
a well-known and respected virologist and researcher into ME then at Raigmore
Hospital in Scotland, who stated the following: “The distribution and number
of tender points in fibromyalgia are different from the chronic fatigue syndrome,
and the management of the two conditions is different. Patients with (ME/CFS)
should be advised not to increase their activities gradually until they feel
80% of normal, whereas patients with fibromyalgia may benefit from a regime
of increasing activity” (BMJ 1994:309:1515).

In
1999, Professor Leonard Jason and colleagues published an updated US case
definition for (ME)CFS which seems to have received little attention from
certain UK psychiatrists who are on record as believing that “CFS/ME” is a
psychosocial disorder and who regard the many abnormalities present in the
disorder as inconsequential. This 1999 US case definition makes two points
of particular and current relevance to the MRC PACE trials:

“If
a person with chronic fatigue syndrome specifies a large number of physical
problems caused by this illness, these physical problems might also make the
person eligible for a diagnosis of somatization disorder, depending upon the
accuracy of the diagnostician. Fibromyalgia Syndrome (FMS) and Multiple Chemical
Sensitivity (MCS) represent additional illnesses of interest where issues
of diagnostic accuracy are concerned”. (JCFS:1999:5:3-33).

In
the interests of evidence-based medicine, those involved with the MRC PACE
trials may wish to reflect upon the available evidence, given that long-established
elementary rules of procedure demand that those undertaking research are normally
required before proceeding to define the proposed topic and to produce a comprehensive
review of the relevant literature: only by so doing can they place themselves
in a position to ensure that their own prospective contribution represents
a potentially useful and original development of knowledge that is based squarely
on the foundations of existing knowledge.

By
proposing to proceed as if a substantive body of mainstream knowledge did
not exist, those involved lay themselves open to suspicions of ignorance and
/ or disingenuousness, or even frank intellectual dishonesty.

As
has been previously noted, investigators are, of course, always at liberty
to take issue with established knowledge, but if they wish to do so legitimately
and credibly, they need to provide a reasoned critique of each tenet of established
knowledge from which they propose to depart and to provide convincing arguments
to show that the proposed research strategy will move understanding and knowledge
along and will not simply reinforce existing confusion.

For
convenience, information already provided for the MRC PACE trial investigators
about the most recognised differences between ME/CFS and FM is reproduced
and summarised here:

In respect of
the MRC CFS trials, there are known and established differences between FM
and ME/CFS and many believe that the FM community and the ME/CFS community
have a right to know why patients suffering from both disorders are to be
amalgamated in the MRC trials that claim to be studying “CFS”.

Likewise, an
explanation is required as to why GPs are suddenly to be offered financial
incentives to identify and refer people with FM to the new CFS centres specifically
so that such patients can be entered into the MRC studies of “CFS”.

It is a matter
of record that Whiting et al expressly excluded FM studies from the systematic
review of the literature that was commissioned by the Policy Research Programme
of the Department of Health and carried out by the Centre for Reviews and
Dissemination at the University of York for the CMO’s Working Group on CFS,
the results of the systematic review being intended to underpin the conclusions
of that report (namely that cognitive behavioural therapy, including graded
exercise regimes, is the management of choice for patients with chronic fatigue
syndrome). The systematic review is unequivocal: “Studies including patients
with fibromyalgia were not selected for the review”; why, therefore, and
on what evidence, was it decided to include patients with FM in the subsequent
MRC trials of CBT on a CFS population? (see Interventions for the Treatment
and Management of Chronic Fatigue Syndrome. Penny Whiting et al. JAMA
2001:286:11:1360-1368).

Of
foremost significance is the fact that fibromyalgia is classified as a distinct
entity in ICD-10 at section M79.0 under Soft Tissue Disorders and it is not
permitted for the same condition to be classified to more than one rubric,
since ICD categories are mutually exclusive.

The
literature itself is quite clear about this distinction, stating that up to
70% of those with ME/CFS have concurrent FM, and those who have both
FM and ME/CFS have worse physical functioning than those who have ME/CFS
alone.

Some
illustrations from the literature make these distinctions clear:

1991:
in spite of some overlap, FM and ME/CFS do not represent the same syndrome.
(Primary fibromyalgia and the chronic fatigue syndrome. AJ Wysenbeek et al
Rheumatology Int 1991:10:227-229)

1998:“recent studies suggest that (co-existent FM and (ME)CFS) may bode much
more poorly for clinical outcome than CFS alone. In contrast to (significantly)
elevated CBG (cortisol binding globulin) levels in patients with CFS, no differences
were observed in FM patients. Differences in secretion ofAVP may explain
the divergence of HPA axis function in FM and (ME)CFS”(Evidence for
and Pathophysiologic Implications of HPA Axis Dysregulation in FM and CFS.
Mark A Demitrack and Leslie J Crofford. Ann New York Acad Sci 1998:840:684-697)

1998:
there is no evidence for elevated Substance P in patients with ME/CFS, whereas
levels are elevated in patients with FM (CFS differs from FM. No evidence
for altered Substance P in cerebrospinal fluid of patients with CFS. Evengaard
B et al Pain 1998:78:2:153-155)

Consultant rheumatologists
who have sufficient experience with both syndromes have observed clinically
that in FM, the muscle pain is helped by gentle stretching and exercise, whereas
in ME/CFS, exercise makes muscle pain worse.

If the Oxford
criteria are to be used for the MRC “CFS” trials, on what logic (other than
a pre-determined agenda) can patients with FM, a completely separate disorder,
be intentionally included from the outset?

Is the MRC entirely
content that the PACE trial proposal also states “Those subjects who also
meet the criteria for “fibromyalgia” will be included”, given that FM
is classified by the WHO as a quite separate disorder from ME/CFS, with a
discrete biomedical profile that is entirely distinct from that found in ME/CFS?

Importantly,
on 3rd June 1998, Baroness Hollis from the then Department of Social
Security sent a letter to Lindsay Hoyle MP (reference POS(4) 3817/88) which
says “The Government recognises that fibromyalgia syndrome (FMS) is a condition
which can cause a wide variety of disabilities from mild to severe. In some
cases it can be a very debilitating and distressing condition. People with
FMS who need help with personal care, or with getting around because they
have difficulty in walking, can claim Disability Living Allowance to help
with meeting related expenditure”. From this letter, it is clear that Government
already recognises fibromyalgia as a distinct entity.

Further, in
the CMO’s UPDATE of August 2003 (a paper communication from the CMO sent to
all doctors in England) entitled “Improving Services for Patients” there is
an item called “Fibromyalgia – A Medical Entity”. This means that the CMO
considers fibromyalgia to be a separate, stand-alone medical entity (and the
fact that it is designated a “medical” disorder means that it is not considered
to be “psychiatric” disorder).

How can the
deliberate inclusion of patients with fibromyalgia in trials that purport
to be studying “CFS” not result in skewed and meaningless conclusions when
the patients being entered in the PACE trials are, from the outset, not clearly
defined?